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https://www.readbyqxmd.com/read/29244080/quantification-of-methadone-and-main-metabolites-in-nails
#1
Teresa Patrícia Magalhães, Sara Cravo, Diana Dias da Silva, Ricardo Jorge Dinis-Oliveira, Carlos Afonso, Maria de Lourdes Bastos, Helena Carmo
The quantification of drugs of abuse in keratinized matrices is becoming of special relevance for monitoring consumption and for post-mortem investigations. We aimed to implement an analytical method for the simultaneous detection of morphine (MORF), 6-monoacetylmorphine (6-MAM), methadone (MET), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrrolidine (EMDP) in nails. After decontamination, the nail samples (30 mg) were submitted to an alkaline digestion followed by a two-step liquid-liquid and SPE extraction using mixed-mode cation exchange cartridges...
December 13, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29241093/quantitative-analysis-of-drugs-in-hair-by-uhplc-high-resolution-mass-spectrometry
#2
Robert Kronstrand, Malin Forsman, Markus Roman
Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h...
December 8, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29216524/multiple-fatalities-in-the-north-of-england-associated-with-synthetic-fentanyl-analogue-exposure-detection-and-quantitation-a-case-series-from-early-2017
#3
Laura Hikin, Paul R Smith, Eleanor Ringland, Simon Hudson, Stephen R Morley
BACKGROUND: Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). METHODS: Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry...
November 29, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29201010/microglia-and-brain-plasticity-in-acute-psychosis-and-schizophrenia-illness-course-a-meta-review
#4
REVIEW
Livia J De Picker, Manuel Morrens, Steven A Chance, Delphine Boche
Objective: Schizophrenia poses a tremendous health, social, and economic burden upon patients and society, indicating current treatment options remain inadequate. Recent findings from several lines of evidence have pointed to the importance of immune system involvement in not only premorbid neurodevelopmental but also subsequent symptom generation and aging processes of brain change in schizophrenia. In this meta-review, we use the summarized evidence from recent quantitative systematic reviews (SRs) and meta-analyses of several subspecialties to critically evaluate the hypothesis that immune-related processes shape the symptomatic presentation and illness course of schizophrenia, both directly and indirectly through altered neuroplasticity...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29190510/predicted-activity-of-ugt2b7-abcb1-oprm1-and-comt-using-full-gene-haplotypes-and-their-association-with-the-cyp2d6-inferred-metabolizer-phenotype
#5
Frank R Wendt, Antti Sajantila, Bruce Budowle
The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous toxins in ante- and post-mortem patients but only represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping approaches, a more comprehensive tramadol metabolism profile has not been evaluated...
November 26, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29187753/subchronic-olanzapine-exposure-leads-to-increased-expression-of-myelination-related-genes-in-rat-fronto-medial-cortex
#6
Kari M Ersland, Silje Skrede, Christine Stansberg, Vidar M Steen
Schizophrenia is a psychotic disorder with severe and disabling symptoms, such as hallucinations, delusions, blunted affect and social withdrawal. The neuropathology remains elusive, but disturbances in immunity-related processes, neuronal connectivity and myelination have consistently been linked to schizophrenia. Antipsychotic drugs can be efficient in reducing symptoms, acting primarily on the dopamine system, but additional biological targets are likely to exist. Here we have screened for novel mechanisms of action in an animal model, using adult rats exposed to long-acting olanzapine, achieving stable and clinically relevant antipsychotic drug concentrations...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29178465/detection-of-human-immunodeficiency-virus-hepatitis-c-virus-and-hepatitis-b-virus-in-post-mortem-blood-specimens-using-infectious-disease-assays-licensed-for-cadaveric-donor-screening
#7
Melissa A Greenwald, Stephen Kerby, Kori Francis, Anna C Noller, William T Gormley, Robin Biswas, Richard A Forshee
BACKGROUND: Evaluation of assay performance on post-mortem blood specimens (obtained after cessation of the heartbeat) presents unique scientific and regulatory challenges. In the United States, assay performance is evaluated in part by spiking postmortem specimens. METHODS: Fifty-four specimens obtained from decedents known to be infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), including some coinfections, were tested for each virus using Food and Drug Administration (FDA)-licensed donor screening tests for nucleic acid, antibody, and antigen...
November 27, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29175501/choice-of-a-suicide-method-trends-and-characteristics
#8
Kairi Kõlves, Matthew McDonough, David Crompton, Diego de Leo
The aim of this study was to examine (1) suicide trends by most prevalent methods in Queensland, Australia, during 2000-2015, and (2) characteristics of people by choice of suicide method in 2000-2013. Data were obtained from the Queensland Suicide Register, which includes police and toxicology reports, post-mortem autopsy and Coroner's findings. Poisson and Joinpoint regression were used to study the first aim, and uni-variate and multi-variate logistic regression analyses were applied to investigate the second aim...
November 15, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29159046/imaging-of-glia-activation-in-people-with-primary-lateral-sclerosis
#9
Sabrina Paganoni, Mohamad J Alshikho, Nicole R Zürcher, Paul Cernasov, Suma Babu, Marco L Loggia, James Chan, Daniel B Chonde, David Izquierdo Garcia, Ciprian Catana, Caterina Mainero, Bruce R Rosen, Merit E Cudkowicz, Jacob M Hooker, Nazem Atassi
Background: Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives: To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods: Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET)...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29151989/human-induced-pluripotent-stem-cells-and-the-modelling-of-alzheimer-s-disease-the-human-brain-outside-the-dish
#10
REVIEW
Godwin Tong, Pablo Izquierdo, Rana Arham Raashid
Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29119924/deaths-in-the-lesbian-gay-bisexual-and-transgender-united-kingdom-communities-associated-with-ghb-and-precursors
#11
John M Corkery, Barbara Loi, Hugh Claridge, Christine Goodair, Fabrizio Schifano
Background Misuse of gammahydroxybutrate (GHB) and its prodrugs gammabutyrolactone (GBL) and 1,4 butanediol (1,4-BD) has increased greatly since the early 1990s, particularly amongst lesbian, gay, bisexual and transgender (LGBT) individuals in recreational and sexual settings, e.g. 'chemsex'. Objective and method This paper presents an overview of GHB pharmacotoxicology and provides analyses of cases in the LGBT population associated with use of these substances extracted from the UK's National Programme on Substance Abuse Deaths database, to which notification is voluntary...
November 8, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29021222/the-perivascular-pathways-for-influx-of-cerebrospinal-fluid-are-most-efficient-in-the-midbrain
#12
Howard Dobson, Matthew MacGregor Sharp, Richard Cumpsty, Theodore P Criswell, Tyler Wellman, Ciara Finucane, Jenna M Sullivan, Roy O Weller, Ajay Verma, Roxana O Carare
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial basement membranes of arteries. This project tested the hypotheses that pial-glial basement membranes of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF...
October 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#13
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28977413/identification-of-the-synthetic-cannabinoid-1-4-cyanobutyl-n-2-phenylpropan-2-yl-1h-indazole-3-carboxamide-cumyl-4cn-binaca-in-plant-material-and-quantification-in-post-mortem-blood-samples
#14
Oya Yeter
In May 2016, a new type of synthetic indazole-3-carboxamide cannabinoid (CUMYL-4CN-BINACA) was detected in seized plant material submitted to the Istanbul Council of Forensic Medicine by the National Police Office. The major ingredient in this material was purified using preparative liquid chromatography, and its structure was identified using liquid chromatography-high-resolution mass spectrometry (LC-HR/MS), gas chromatography-electron ionization/mass spectrometry (GC-EI/MS), nuclear magnetic resonance (NMR) spectroscopy and Fourier transform-infrared spectroscopy (FT-IR)...
August 31, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28973645/alpha-synuclein-induces-the-unfolded-protein-response-in-parkinson-s-disease-snca-triplication-ipsc-derived-neurons
#15
Sabrina M Heman-Ackah, Raquel Manzano, Jeroen J M Hoozemans, Wiep Scheper, Rowan Flynn, Wilfried Haerty, Sally A Cowley, Andrew R Bassett, Matthew J A Wood
The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting from triplication of the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution to the molecular pathogenesis of PD. We used the double-nicking CRISPR/Cas9 system to conduct site-specific mutagenesis of SNCA in these cells, generating an isogenic iPSC line with normalized SNCA gene dosage. Comparative gene expression analysis of neuronal derivatives from these iPSCs revealed an ER stress phenotype, marked by induction of the IRE1α/XBP1 axis of the unfolded protein response (UPR) and culminating in terminal UPR activation...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28942032/post-mortem-review-of-fentanyl-related-overdose-deaths-among-identified-drug-users-in-southern-bavaria-germany-2005-2014
#16
Inga Sinicina, Hans Sachs, Wolfgang Keil
BACKGROUND: Two decades ago, there were only single case reports on deaths in Europe following the consumption of illicitly manufactured fentanyl by problem drug users. Today, lethal fentanyl intoxication is now no longer a rarity. Since 2005, a rapid increase of lethal fentanyl-related intoxications in the drug scene has been observed at the Institute of Legal Medicine, Ludwig Maximilians University, Munich. We hypothesized that this rise is the result of the launch of fentanyl matrix patches in Germany in 2004, their broad acceptance, their diversion from the regulated supply chain, and incautious prescription by medical care providers...
September 14, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28941755/the-diagnostic-value-of-fdg-and-amyloid-pet-in-alzheimer-s-disease-a-systematic-review
#17
REVIEW
Louise Rice, Sotirios Bisdas
PURPOSE: By 2050 it is projected that 115 million people worldwide will have Alzheimer's Disease (AD) [1]. Recent attempts have been made to redefine the diagnostic criteria of AD to include markers of neurodegeneration - measurable by FDG-PET - and markers of amyloid accumulation - measurable by amyloid-PET. MATERIALS AND METHODS: A systematic review of the literature was performed to examine the current diagnostic use of amyloid and FDG PET. MEDLINE and EMBASE databases and the Cochrane Database were searched for relevant papers RESULTS AND DISCUSSION: This search resulted in twenty-nine papers on amyloid imaging, twenty-three papers on FDG-PET and eight papers which utilized both techniques...
September 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28924203/the-common-variants-implicated-in-microstructural-abnormality-of-first-episode-and-drug-na%C3%A3-ve-patients-with-schizophrenia
#18
H Y Ren, Q Wang, W Lei, C C Zhang, Y F Li, X J Li, M L Li, W Deng, C H Huang, F Du, L S Zhao, Y C Wang, X H Ma, X Hu, T Li
Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894300/striatal-dopamine-d1-type-receptor-availability-no-difference-from-control-but-association-with-cortical-thickness-in-methamphetamine-users
#19
K Okita, A M Morales, A C Dean, M C Johnson, V Lu, J Farahi, M A Mandelkern, E D London
Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28893562/positive-allosteric-modulation-of-m1-and-m4-muscarinic-receptors-as-potential-therapeutic-treatments-for-schizophrenia
#20
REVIEW
Samantha E Yohn, P Jeffrey Conn
Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia...
September 9, 2017: Neuropharmacology
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